We have recently discovered the presence of a lectin-like substance in the serum of cystic fibrosis (CF) patients and their parents (obligate heterozygotes). Lectins are proteins that have specific abilities to agglutinate cells, percipitate glycoproteins and to stimulate mucus release. The assay we have developed employs specific agglutination of mouse-erythrocytes, and lends itself to a rapid screening test to detect carriers of the CF gene. This research project will study further the reliability and usefulness of this screening test, and will attempt to modify it to enable specific identification of homozygotes vs heterozygotes. The lectin will be isolated from CF serum and its characteristics and structure will be studied. We will prepare an antibody against the lectin and study the most likely site of synthesis of the lectin by immunologic techniques. The potential role of the lectin in the pathogenesis of cystic fibrosis will be studied by evaluating its effects on mucus-secreting cells and parotid secretion in an appropriate animal model, and on various glycoproteins and bacterial suspensions. Finally, we will evaluate the use of specific inhibitors of this lectin as therapeutic agents in cystic fibrosis. Thus, the major objectives of this research proposal are to develop a simple and reliable test for detecting the CF gene in carriers, and to determine the underlying pathogenetic factor causing the disease.